Graft copolymers and method to prepare same

ABSTRACT

A thermally processable graft copolymer formed from a water soluble polymer and a water insoluble polymer, wherein the graft copolymer forms a hydrogel upon exposure to water. A method to form such a hydrogel-forming graft copolymer by copolymerizing a water soluble 2-substituted-2-oxazolines with a water insoluble 2-substituted-2-oxazoline. A method to form such a hydrogel-forming graft copolymer by transamidating a poly-2-oxazoline with a carboxylic acid terminated water-insoluble polymer.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Application is a Divisional Application claiming priority to theApplication having Ser. No. 10/603,564, filed Jun. 25, 2003, now U.S.Pat. No. 7,030,202.

FIELD OF THE INVENTION

Applicants' invention comprises polyoxazoline-based thermoplastic,polymeric hydrogel compositions that can be formed into useful articlesby conventional molding processes, such as injection molding,compression molding, and extrusion, wherein those molded articles havethe properties of a hydrogel material. Applicants' invention furthercomprises two methods for forming these novel thermoplastic, polymerichydrogel compositions.

BACKGROUND OF THE INVENTION

Hydrogel-forming polymers are those which are not water soluble, butwhich upon contacting aqueous fluids, imbibe such fluids. Upon absorbingwater, the mechanical properties of articles formed from such polymerichydrogel materials change. For example, articles which are rigid whendry may become soft and pliable when wet.

Certain of these systems are used in commerce ranging from use as“supersorbers” in baby diapers to more sophisticated uses in themanufacture of soft contact lenses. Polymer hydrogel systems includeionically linked hydrogels, covalently crosslinked hydrogels, and thelike.

Ionic hydrogels are polymers containing functional groups that ionicallybond to form a crosslinked system. Such materials are used to form toyproducts that can be continuously reformed and reshaped. Thesematerials, however, cannot be formed into a permanent shape orconfiguration.

Covalently crosslinked hydrogels are formed by crosslinking otherwisewater-soluble polymers. Once these materials are crosslinked, they willno longer dissolve in water, or in any other solvent for that matter.Nevertheless, these crosslinked materials will absorb water and swell indimension. Compositions such as crosslinkedpoly-2-hydroxyethylmethacrylate are used to form contact lenses. Thesematerials, however, cannot be thermally processed.

Mechanically crosslinked systems are formed when two polymers which areincompatible are chemically linked as either block copolymers or graftcopolymers. On the one hand, if the two incompatible homopolymers aresimply blended together, a gross phase separation occurs. If on theother hand, the two polymers or connected together covalently, amicrophase separation occurs.

This microphase separation is a well known phenomenon that has beenutilized, most notably, in the styrene-butadiene Kraton triblock rubberfield. Block copolymers partition into different phases, a continuousphase consisting of the higher percentage polymer and a discontinuous ordispersed phase consisting of the lower percentage polymer. Thedispersed phase can form very distinct domains, including spheres,cylinders, and lamella. The configuration of these domains is related tothe relative percentages of the two phases. At low percentages, thedispersed phase comprises spherical domains. As that percentageincreases the dispersed phase forms cylindrical domains and finallydiscrete lamella.

Significantly, a microphase separated two-component polymeric materialexhibits two glass transition temperatures (t_(g)'s), namely one foreach polymer present. When the temperature of the composite material isbelow the respective glass transition temperatures of both components,the copolymer is rigid. If the composite material is warmed above theglass transition temperatures of both phases, the copolymer will flow.Therefore, such a mechanically crosslinked copolymer can be thermallyprocessed using conventional molding techniques such as extrusion andinjection molding.

A mechanically crosslinked hydrogel copolymer comprises a block or graftcopolymer formed from incompatible polymers where the continuous phaseis a water soluble polymer. Various water soluble organic polymersprepared from substituted ethylenes are known, includingpolyvinylpyrrolidone, polyvinylalcohol, and the like. Polyethylenimine,and certain of its derivatives is also water soluble.

Poly-2-alkyl-2-oxazolines, where the alkyl group comprises 1-5 carbons,are such water soluble, N-acyl polyethyleneimines. Significantly, thesepoly-2-alkyl-2-oxazolines have thermal properties that differ materiallyfrom water soluble polymers prepared from substituted ethylenes. Forexample, poly-2-ethyl-2-oxazoline has both a low dry glass transitiontemperature of 70-71° C. and a high thermal degradation temperatureabove 380° C.

Prior art mechanically crosslinked hydrogel systems do not includesystems based upon poly-2-alkyl-2-oxazolines. U.S. Pat. No. 4,582,877,in the name of Fairchok et al., teaches a method to enhance thewettability of polypropylene by blending polypropylene with substitutedpolyethyleneimines. Fairchok et al. teaches preparation of thosesubstituted polyethyleneimines by reacting a poly-2-oxazoline with acarboxylic acid to form a polyethyleneimine having pendent groups of upto 22 carbon atoms. Col. 1/1. 50 to Col. 2/1. 17. Each such 22 carbonpendent side group would increase the molecular weight of thepolyethyleneimine by only about 300 grams/mole. In a most preferredembodiment, Fairchok et al. teaches preparation of a covalentlycrosslinked material by reacting a poly-2-oxazoline with a polybasiccarboxylic acid. Col. 2/1. 18-25.

In contrast, Applicant's invention comprises a graft copolymercomprising a water soluble poly-2-alkyl-oxazoline having a plurality ofpendent non-water soluble polymers grafted thereon, wherein each of thependent non-water soluble polymers has a number average molecular weightof at least 5,000. Moreover, Applicants' invention does not encompassany covalently crosslinked systems.

SUMMARY OF THE INVENTION

In a first embodiment, Applicants' novel invention comprises a thermallyprocessable graft copolymer formed from a water soluble polymer and awater insoluble polymer, wherein that graft copolymer forms a hydrogelupon exposure to water. The water soluble portion of Applicants' novelgraft copolymer is formed from a poly-2-substituted-2-oxazoline. Thewater insoluble portion of the graft copolymer is formed from apolyalkyleneoxide polymer/copolymer, long chain alkyl, polybutadiene,polyisoprene, a polyester, a polyamide, or a polyurethane.

A second embodiment of the instant invention comprises a novel method toform such a hydrogel-forming graft copolymer by copolymerizing a first2-substituted-2-oxazolines with a second 2-substituted-2-oxazoline. Sucha copolymerization can be performed neat or in solution.

A third embodiment of Applicants' invention comprises a novel method toform such a hydrogel-forming graft copolymer by transamidating apoly-2-oxazoline with a carboxylic acid terminated water-insolublepolymer. In the alternative, an amide exchange reaction is performedusing a polymeric acid chloride, a polymeric acid salt, or a polymericanhydride.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood from a reading of the followingdetailed description taken in conjunction with the drawings in whichlike reference designators are used to designate like elements, and inwhich:

FIG. 1 is a perspective view depicting the structure of Applicants'novel graft copolymer according to the present invention; and

FIG. 2 is a perspective view depicting the configuration of Applicants'novel graft copolymer in an aqueous environment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIG. 1, applicants' invention is shown as graft copolymersystem 10, which comprises a water soluble polymer 12 having one or morependent non-water soluble polymers 14 and 16 grafted thereon. AlthoughFIG. 1 depicts two non-water soluble polymers, i.e. polymer 14 andpolymer 16, grafted onto water soluble polymer 12, Applicants' inventionincludes graft copolymers in which a plurality of non-water solublepolymers are grafted onto a water soluble polymer backbone.

Turning to FIG. 2, the configuration of three different copolymer chainsin an aqueous environment is shown. The water soluble portions of thesecopolymers, i.e. 12(a), 12(b), and 12(c), remain individually dispersedin the solvent. The water insoluble portions, however, aggregate to formdiscrete domains 18(a), 18(b), and 18(c). These dispersed domainsfunction as “mechanical” crosslinks thereby giving copolymer 12 certainphysical properties generally found only in covalently crosslinkedpolymers. Copolymer 12, however, contains no actual covalent crosslinks,and therefore, is thermally processable.

Water soluble portion 12 of graft copolymer 12 comprises a substitutedpoly-N-acyl-ethyleneimine having structure I

wherein R₁ is a hydrogen or an alkyl group having 1 to 4 carbons.Polymer I has a number average molecular weight of between about 5,000to about 1,000,000, preferably between about 10,000 to about 100,000,and most preferably between about 25,000 and about 75,000. Substitutedpolyethyleneimine I is prepared by a cationic ring openingpolymerization of 2-R₁-2-oxazoline

III using catalyst IV, where R′ is hydrogen, alkyl, aralkyl, andmixtures thereof, and X is acetate, p-tosylate, halide, sulfate,triflate, and mixtures thereof. For example, methyl triflate can be usedas initiator IV, in which case R′ is methyl and X is triflate. Thecationic ring opening polymerization of monomer III can be conductedneat or in solvent. Solvents for this ring opening polymerizationinclude orthodichlorobenzene, ethyl benzene, cumene, xylene, decane,2-ethyl hexyl acetate, naphthalene, and octane. For example, thepolymerization can be carried out in orthodichlorobenzene at atemperature between about 7° C. and about 180° C.

In a most preferred embodiment, R₁ is ethyl, and polymer I has a numberaverage molecular weight of about 50,000. This poly-2-ethyl-2-oxazolinepolymer is sold commercially under the name of AQUASOL 50 by PolymerChemistry Innovations, Inc., the assignee of this application.

To form the mechanically crosslinkable polymeric hydrogel of the presentinvention, up to about 20% of the pendent R₁ groups on polymer I arereplaced by a water soluble polymer to form a graft copolymer ofstructure II

The WATER INSOLUBLE POLYMER portion of graft copolymer II is a non-watersoluble polymeric material having a number average molecular weightbetween about 5,000 and 100,000, preferably between about 8,000 andabout 20,000, and most preferably between about 10,000 and 15,000. TheWATER INSOLUBLE POLYMER includes polyethylene, long chain alkyl,polypropylene, polybutadiene, polyisoprene, polystyrene,polymethylacrylate, polymethylmethacrylate, polyurethanes, polyamides,polyesters, polyesteramides, and copolymers of same.

In a first embodiment, graft copolymer II is formed by a transamidationreaction. In general, transamidation is accomplished by reacting anamide of one carboxylic acid with a second carboxylic acid. A mixture ofamides usually results. For example, if amide V is reacted withcarboxylic acid VI, transamidation occurs to yield a mixture of amides Vand VII.

If carboxylic acid VIII is removed from the reaction as it forms,however, the equilibrium will be continuously shifted to produce moreamide VII. Therefore, amide V can be essentially completely converted toamide VII if acid VIII is removed as it forms.

A similar amide exchange reaction can also be performed by reacting anamide of a first carboxylic acid with a second acid salt, a second acidchloride, and/or a second acid anhydride. The transamidation reactionsdiscussed below used to prepare graft copolymers can also use apolymeric acid salt, a polymeric acid chloride, and/or a polymeric acidanhydride.

Graft copolymer II, where the WATER INSOLUBLE PORTION comprisespolystyrene, polybutadiene, polyisoprene, polymethylacrylate,polymethylmethacrylate, or copolymers of

same, is formed by reacting polymer I with a carboxylic acid terminatedpolymer having structure IX. Polymer IX can be prepared by ananionically catalyzed polymerization. For example, where R₂ is phenyl,ethylenyl, isopropenyl, or carbomethoxy, and R₃ is either hydrogen ormethyl, water-insoluble polymer XII can be formed by an anionicpolymerization of monomer X to yield lithium-terminated living polymerXI which is reacted with carbon dioxide to give lithium carboxylateterminated polymer XII.

Reaction of one mole of polymer I where R₁ is ethyl with 0.20 moles ofacid terminated polymer XII where R₂ is phenyl and R₃ is hydrogen, alongwith removal of the proprionic acid formed, will yield a graft copolymerhaving the structure XIII. Preferably, the number average

molecular weight of graft copolymer XIII is between about 1,000 andabout 10,000,000 with m being between about 1 and about 10,000Alternatively, the WATER INSOLUBLE PORTION of graft copolymer II cancomprise a polyethyleneoxide, a polypropyleneoxide, or apolyethyleneoxide-co-polypropylene oxide. Such a graft copolymer isprepared by a transamidation reaction of polymer I with a carboxylicacid terminated polyalkyleneoxide polymer or copolymer.

A carboxylic acid terminated polyethylene oxide polymer can be preparedby anionic ring opening polymerization of ethylene oxide XIV to givelithium-terminated polyethylene oxide XV (R₁₀ is hydrogen).Lithium-terminated polyethyleneoxide XV is reacted with acrylic acid andthen quenched to give acid terminated polyethylene oxide XVI.

Graft copolymer II can be formed by partial transamidation of polymer Iwith polymer XVI. As an example, 0.20 moles of carboxylic acidterminated polyethyleneoxide XVI (R₁₀=H) are reacted with 1.0 moles ofpolymer 1 (R1=ethyl), with removal of the proprionic acid as it forms,to prepare graft copolymer XVII.

The WATER INSOLUBLE PORTION of graft copolymer II prepared bytransamidation can also comprise a polyester or a polyamide. Carboxylicacid terminated polyester XXI can be prepared by reacting between about0.1 to about 0.2 equivalents of monofunctional alcohol XVIII, 1.0equivalents of diacid XIX, and between about 0.8 to about 0.9equivalents of diol XX. Preferably diacid XIX comprises adipic acid,i.e. q is 4, and diol XX comprises hexanediol, i.e. r is 6.

Graft copolymer II, where the WATER INSOLUBLE POLYMER comprises apolyester can be prepared by partial transamidation of polymer I withcarboxylic acid terminated polyester XXI to give a graft copolymerhaving a number average molecular weight of between about 1,000 andabout 10,000,000 with s being between about 2 and about 1,000,000.

In a second embodiment, graft copolymer II can be prepared bycopolymerization rather than by transamidation. For example, monomer IIIand monomer XXII can be copolymerized to form graft copolymer II.

As in the transamidation embodiment discussed above, the WATER INSOLUBLEPOLYMER portion of monomer XXII is selected from the group consisting ofpolyesters, polyamides, polyesteramides, polyurethanes,polyethyleneoxide, polypropyleneoxide,polyethyleneoxide-co-polypropyleneoxide, polybutadiene, polyisoprene,polymethylacrylate, polymethylmethacrylate, polystyrene, and copolymersof same.

Where the WATER INSOLUBLE POLYMER portion comprises polybutadiene,polyisoprene, polymethylacrylate, polymethylmethacrylate, orpolystyrene, monomer XXII can be prepared by using the lithium salt of2-methyl-2-oxazoline as an anionic polymerization initiator.

Lithium diisopropylamide XXIII can be prepared by adding a 1.5 Msolution of n-BuLi in THF to diisopropylamine in THF at 0° C. Afterabout 30 minutes that solution can be cooled to −78° C. and transferredvia cannula to a precooled solution of 2-methyl-2-oxazoline in THF at−78° C. to form initiator XXIV. Initiator XXIV is added to an excess ofanionically-polymerizable monomer to form a lithium-terminated polymerwhich after quenching with an acid yields 2-substituted-2-oxazoline XXV.

Copolymerization of 1.0 moles of monomer III where R₁ is ethyl with 0.20moles of monomer XXV where R₂ is hydrogen and R₃ is phenyl yields graftcopolymer XIII. This copolymerization can be performed neat or insolvent.

As those skilled in the art will appreciate, a carboxylic acidterminated polyamide can be similarly formed from a condensationreaction of about 0.1 to about 0.2 equivalents of a monoamine, 1.0equivalents of a diacid, and about 0.8 to about 0.9 equivalents of adiamine, with continuous removal of the water formed. Moreover, reactionof about 0.1 equivalents of a monoamine, 1.0 equivalents of a diacid,and about 0.8 to about 0.9 equivalents of a mixture of a diol anddiamine, will form a carboxylic acid terminated polyesteramide.

In order to prepare graft copolymer II where the WATER INSOLUBLE POLYMERcomprises a polyalkyleneoxide polymer or copolymer, initiator XXIV canbe used to anionically polymerize ethylene oxide (XIV with R₁₀=H) and/orpropylene oxide (XIV with R₁₀=methyl) to form 2-polyethyleneoxide-2-oxazoline XXIX (R₁₀=H), 2-polypropylene oxide-2-oxazoline XXIX(R₁₀=methyl), or 2-polyethyleneoxide-co-polypropyleneoxide-2-oxazolineXXX. As those skilled in the art will appreciate, 2-oxazoline-terminatedcopolymer XXX may comprise a random copolymer of ethylene oxide unitsand propylene oxide units, or a block copolymer of alternating ethyleneoxide blocks and propylene oxide blocks.

Monomer XXIX can be copolymerized with monomer III to form graftcopolymer II. The cationic ring-opening copolymerization can be carriedout neat or in solvent. For example, copolymerizing 1.0 moles of monomerIII, where R₁ is ethyl, with 0.20 moles of monomer XXIX, where R₁₀ ishydrogen, forms graft copolymer XXXI.

Alternatively, copolymerization of monomer XXXIII with monomer III givesa graft copolymer where the WATER INSOLUBLE POLYMER portion comprises apolyester. Carboxylic acid terminated polyester XXI is reacted withethanolamine to form beta-hydroxyamide terminated polyester XXXII whichis subsequently cyclized with removal of one mole of water to formmonomer XXXIII.

Preferably, the graft copolymer formed by the cationic ring-openingcopolymerizing monomer III, where R₁ is ethyl, and monomer XXXIII, whereq is 4 and r is 6, has a number average molecular weight between about100 and about 10,000,000 with s being between about 2 and about1,000,000.

While the preferred embodiments of the present invention have beenillustrated in detail, it should be apparent that modifications andadaptations to those embodiments may occur to one skilled in the artwithout departing from the scope of the present invention as set forthin the following claims.

1. A polymeric composition having the structure

wherein R₁ is selected from the group consisting of hydrogen, methyl,ethyl, and propyl, X is selected from the group consisting of acetate,p-tosylate, halide, sulfate, triflate, and mixtures thereof, andPOLYMER2 is a water-insoluble polymeric material having an averagemolecular weight in excess of 5,000; wherein POLYMER2 has the structure:

wherein R₄ is selected from the group consisting of hydrogen, methyl,and mixtures thereof, and R₅ is hydrogen or alkyl; and wherein n isbetween about 50 to about 10,000, m is adjusted such that m/(n+m) isbetween about 0.0001 to about 0.20, and p is between about 60 to about1250.